The overall objective of this project is to continue the evaluation of the theory that deficiency in central neurotransmitters is related to the genesis and evolution of cognitive impairment in senile dementia. Specifically, we will evaluate further the hypothesis that deficiency in availability of brain acetylcholine (ACh) is related to senile dementia of the Alzheimer's type (SDAT). This will be done by studying the effects of agents which enhance cholinergic functioning. The rationale is based on evidence that the cholinergic system is directly involved in the memory process; that a selective loss of cholinergic neurons and of the ACh synthesizing enzyme, CAT occurs in SDAT; and that administration of dietary choline or lecithin elevates brain levels and activity of ACh. A total of about 100 healthy outpatients (aged 60-85) with mild to moderate SDAT will be studied. We will conduct a series of studies to evaluate the effects single doses of the ACh precursor lecithin; the acetylcholinesterase inhibitor physostigmine; the muscarinic receptor agonist arecoline; lecithin plus physostigmine; and lecithin plus arecoline. Twenty patients will be assigned to each study. A double-blind crossover design will be employed, with treatment days spaced 1 week apart. The optimal doses of these agents will first be determined on an individual basis. The results of the single-dose studies with lecithin, physostigmine and arecoline will indicate which sites of action (presynaptic, synaptic, or postsynaptic) can be successfully manipulated in SDAT, thereby suggesting the best treatment strategy.